This proposal will characterize antibody recognition sites on envelope glycoproteins of human cytomegalovirus (HCMV). Linear and non-linear antibody binding determinants will be mapped using a panel of antisera and murine monoclonal antibodies generated against a collection of overlapping restriction endonuclease fragments of the glycoprotein genes expressed in prokaryotic vectors and a series of truncated glycoproteins expressed in recombinant eukaryotic systems. Strain specific and strain common antibody recognition sites expressed on glycoproteins from clinical HCMV isolates will be studied with the aid of these antigenic maps and antisera (monoclonal antibodies) and a series of recombinant-derived, truncated glycoproteins from these clinical HCMV isolates. In addition, the proposed studies will examine the relation between HCMV strain variability, strain specific immunity and reinfection in human populations. Because antiviral antibodies play an important role in limiting the severity of HCMV-induced disease in many different patient populations, these studies are relevant to our understanding of the pathogenesis of HCMV infections and are essential to the rational design of effective therapies for treatment and/or prevention of HCMV-induced disease.